School of Veterinary Medicine, Faculty of Health and Medical Sciences, VSM Building, University of Surrey, Daphne Jackson Road, Guildford, Surrey GU2 7AL, UK.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9PS, UK.
Cells. 2024 Nov 20;13(22):1926. doi: 10.3390/cells13221926.
A state-of-the-art multi-omics approach was applied to improve our understanding of the aetio-pathogenesis of a highly prevalent, performance-limiting disorder of racehorses: mild-to-moderate equine asthma (MMEA). This is a prerequisite to improving prophylactic, management, and therapeutic options for this condition. Although a number of risk factors have been identified, options for intervention are limited. This study applied a multi-omic approach to reveal key inflammatory pathways involved in inflammatory cell recruitment to the lower airways and highlight distinct MMEA inflammatory profiles. We compared bronchoalveolar lavage fluid (BALF) cell gene and protein expression data from horses with non-inflammatory BALF cytology with those isolated from horses with neutrophilic, mastocytic, mixed neutrophilic/mastocytic, and eosinophilic/mastocytic inflammation. The analyses on transcriptomic/proteomic data derived from BALF from horses with neutrophilic cytology showed enrichment in classical inflammatory pathways, and horses with mastocytic inflammation showed enrichment in pathways involved in hypersensitivity reactions related to nonclassical inflammation potentially mimicking a Th2-immune response. The mixed eosinophilic/mastocytic group also presented with a nonclassical inflammatory profile, whereas the mixed neutrophilic/mastocytic group revealed profiles consistent with both neutrophilic inflammation and hypersensitivity. Our adopted multi-omics approach provided a holistic assessment of the immunological status of the lower airways associated with the different cytological profiles of equine asthma.
采用了一种最先进的多组学方法，以提高我们对马科动物中一种高度流行、表现受限的疾病（马的轻度至中度哮喘，MMEA）的病因发病机制的理解。这是改善这种疾病的预防性、管理性和治疗性选择的前提。尽管已经确定了许多风险因素，但干预的选择有限。本研究采用了多组学方法来揭示参与炎症细胞募集到下呼吸道的关键炎症途径，并强调了不同的 MMEA 炎症特征。我们比较了支气管肺泡灌洗液（BALF）细胞基因和蛋白表达数据，这些数据来自具有非炎症性 BALF 细胞学的马与来自具有中性粒细胞性、肥大细胞性、混合中性粒细胞/肥大细胞性和嗜酸性粒细胞/肥大细胞性炎症的马。来自具有中性粒细胞细胞学的马的 BALF 转录组/蛋白质组数据分析显示，经典炎症途径富集，具有肥大细胞性炎症的马显示出与非经典炎症相关的过敏反应途径富集，可能模拟 Th2 免疫反应。混合嗜酸性粒细胞/肥大细胞组也呈现出非经典炎症特征，而混合中性粒细胞/肥大细胞组显示出与中性粒细胞炎症和过敏反应一致的特征。我们采用的多组学方法提供了对与马哮喘不同细胞学特征相关的下呼吸道免疫状态的整体评估。
